Methods such as a batch method, a dialysis method, a liquid-liquid diffusion method, and a gas-liquid diffusion method have been used for crystallization of biopolymers such as proteins (see Non-Patent Document 1).
Taking the batch method as an example, a precipitant such as ammonium sulfate is directly added to a protein solution until a crystallization concentration is reached. Typically, the precipitant is added to the biopolymer solution in a container, and biopolymer crystals are produced by supersaturating the biopolymer under controlled conditions. The batch method, however, involves certain drawbacks, including large quantities of high-concentration polymer sample, skilled operation and poor repeatability, and difficulties in the screening of crystallization conditions. Further drawbacks of the foregoing crystallization methods are that the methods require relatively specific crystallization conditions for specific polymers, and are not usable under general conditions.
For example, Patent Document 1 discloses a technique in which a protein solution of a preset temperature condition suited for nucleation of protein crystals is irradiated with a laser beam, which is presumably a visible laser beam. The scattering of the laser beam is then analyzed to detect that the protein crystal nucleation has started, upon which the protein solution is brought to a controlled temperature condition suited for crystal growth.
Patent Document 2 discloses a method whereby a solution existing in a supersaturated state but with a low degree of supersaturation (metastable solution) unsuited for protein crystal nucleation is irradiated with the 266 nm fourth harmonic wave of a neodymium YAG laser, or with 500 W xenon lamp light to create crystals of chicken egg white lysozyme.
Patent Document 3 discloses a method for producing a crystal nucleus whereby a solution dissolving the crystallization target solute is irradiated with at least one of a picosecond pulsed laser and a femtosecond pulsed laser to generate a crystal nucleus.
Patent Document 4 discloses a biopolymer crystallization container of a structure in which two or more noble metals and/or two or more materials covered with noble metal are disposed in 1 to 1,000 nm intervals.